Paracrine mechanisms in adult stem cell signaling and therapy

By M. Gnecchi, Zhiping Zhang, Aiguo Ni, V. Dzau. Circulation Research, 2008

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Animal and preliminary human studies of adult cell therapy following acute myocardial infarction have shown an overall improvement of cardiac function. Myocardial and vascular regeneration have been initially proposed as mechanisms of stem cell action. However, in many cases, the frequency of stem cell engraftment and the number of newly generated cardiomyocytes and vascular cells, either by transdifferentiation or cell fusion, appear too low to explain the significant cardiac improvement described. Accordingly, we and others have advanced an alternative hypothesis: the transplanted stem cells release soluble factors that, acting in a paracrine fashion, contribute to cardiac repair and regeneration. Indeed, cytokines and growth factors can induce cytoprotection and neovascularization. It has also been postulated that paracrine factors may mediate endogenous regeneration via activation of resident cardiac stem cells. Furthermore, cardiac remodeling, contractility, and metabolism may also be influenced in a paracrine fashion. This article reviews the potential paracrine mechanisms involved in adult stem cell signaling and therapy.

Subfields: Biomaterials, Genetics, Surgery

View Paper: https://www.semanticscholar.org/paper/6fed9c19b62decda9638e41742a2b2126f94d01e

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Citations in the corpus

Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. (2011, background): “These beneficial effects were shown to be associated with a transient recruitment of MSCs within the kidney with a minimal incorporation in the regenerating tubules [5,40,41].”
Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity (2009, background): “Our findings do not exclude the many other important properties ascribed to MSCs, including extracellular matrix remodeling (11), progenitor cells recruitment (27), and release of paracrine factors (13).”
Harnessing the Mesenchymal Stem Cell Secretome for the Treatment of Cardiovascular Disease (2012, background): “MSCs induce myocardial protection by promoting cardiomyocyte survival and preventing apoptosis through activation of PKC, PI3K/Akt, NF-kB, and STAT3 signaling (Gnecchi et al., 2008; Mirotsou et al., 2011).”
Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine (2017, background): “The third major mechanism is secretion of bioactive factors, which may potentially affect both local and systemic physiological processes [8].”
Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. (2013, neutral): “…and inhibits c-JNK signaling after I/R Paracrine action of MSC secretion has been shown to be mediated via enhanced phosphorylation of survival pathways, especially of PI3K/Akt pathway (Chimenti et al., 2010; Deuse et al., 2009; Gnecchi et al., 2006; Gnecchi et al., 2008; Matsuura et al., 2009).”
Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6 (2009, background): “…less than the effects of i.v. infusions of hMSCs. MSCs in culture and in response to chemokines or injured cells secrete large amounts of therapeutic factors such as TGF-b, HGF, IL-4, IL-10, PGE2, and stanniocalcin-1 (Caplan, 2009; Gnecchi et al., 2008; Block et al., 2009; Ohtaki et al., 2008).”